Functional Outcome In Ischemic Stroke Research Articles

Trends in Sex Differences of Functional Outcome after Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies - including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR) - detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time. To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment. We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome. Among 11840 patients receiving IVT, 2489/5503 (45.4%) women achieved favorable functional outcome compared to 3787/6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjOR 0.87, 95%CI 0.79-0.96, p=0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) 1.04, 95%CI 1.02-1.06, p<0.001) but not in women (adjOR (per year) 1.01, 95%CI 0.99-1.03, p=0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction and longer door-to-needle times were significantly associated with outcome only in women. Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future.Data access statement: Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (DM), access inquiries have to be addressed to the registry's academic review board.

PERIPHERAL ARTERIAL STIFFNESS PREDICTS INDEPENDENTLY FUNCTIONAL OUTCOME AFTER ISCHEMIC STROKE

Objective: Aortic stiffness is a strong predictor of morbidity in various clinical conditions, including ischemic stroke. However, the prognostic significance of the peripheral arterial stiffness, defined as radial -carotid pulse wave velocity - for functional outcome in ischemic stroke remains unknown. Design and method: We enrolled 189 patients (126 males, age 62.9±11.9 years, mean±SD) with acute ischemic stroke (NIHSS score at admission 6.4±5.1 points). Radial-carotid pulse wave velocity (CR PWV), peripheral blood pressure (BP) and heart rate (HR) were measured (SphygmoCor®) within several (6±2) days after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale (mRS) with an mRS score of 0 to 1 considered as an excellent outcome. Results: In univariate analysis, age, severity of stroke, heart rate, previous stroke, predicted stroke functional outcome. By contrast, CR PWV had no significant predictive value for stroke outcome (8.91±1.66 vs 8.56±1.50 m/s; p=0.14). In a multivariate analysis, the predictive value of CR PWV was significantly associated with functional outcome (OR, 1.34; 95% CI, 1.77–1.01; p=0.04) after adjustment for covariates, with higher values of CR PWV being associated with better prognosis. Conclusions: We found that the CR PWV in patients in the subacute phase of ischemic stroke is associated with functional outcome independently of traditional neurologic and hemodynamic factors. This PWV index might be useful in clinical practice, including therapeutic decisions, but needs broader studies in patient populations of stroke subtypes.

In-hospital mortality in patients with ischemic stroke and a large cerebral artery occlusion, who underwent mechanical thrombectomy

Occlusion of a large cerebral artery in ischemic stroke (IS) is associated with a high mortality rate. Despite the results of studies that have demonstrated the beneficial effect of endovascular therapy on functional outcome in IS, little research has been conducted on its impact on hospital mortality in IS, its timing and structure.Objective: to investigate hospital mortality in patients with IS and large cerebral artery occlusion, who underwent mechanical thrombectomy (MTE).Material and methods. The retrospective study included data from 233 patients with IS and confirmed occlusion of a large cerebral artery (internal carotid artery, M1 and M2 segments of the middle cerebral artery, basilar artery) treated at the regional vascular center V.V. Veresaev Hospital, Moscow, 2018 and 2022. A comparison of hospital mortality in the group of patients who underwent MTE and the group of patients who received basic therapy was performed.Results. MTE was performed in 107 patients (46%); 126 patients (54%) received only basic therapy. The mortality rate of all patients included in the study was 44.2%. Among all deaths, the proportion of patients with MTE was only 7.2%, while the proportion of patients on basic therapy was 36.9% (p&lt;0.001). Mortality in the MTE group was four times lower than in the basic therapy group – 15.8% compared to 68.2% (p&lt;0.001). We observed that certain manifestations were significantly more frequent in the basic therapy group: cerebral edema (42% vs. 18.6%), hemorrhagic transformation (19.9% vs. 12.9%), venous thromboembolism (6.3% vs. 3.7%) and infectious complications (42.8% vs. 14.3%). The mortality of patients in the basic therapy group was higher on the first day, on days 2–3 and also on days 4–7, while no differences in mortality were observed after the first week of the disease.Conclusion. Admission of a patient with IS within the “therapeutic window” creates the conditions for a significant reduction in hospital mortality and the incidence of stroke complications.

Risk Factors and Functional Outcome of Ischemic Stroke Vis-à-vis Hemorrhagic Stroke at a Tertiary Care Hospital in North India

Abstract Background: Worldwide, stroke is the most common cause of death after coronary artery disease (CAD). The risk factor stratification and prognostication of stroke patients are vital in planning and allocating health-care resources. Methods: We conducted a prospective, comparative observational study. Fifty age- and sex-matched cases each of ischemic stroke (IS) and intracerebral hemorrhage (ICH) stroke were enrolled, and baseline demographic, risk factor profile, Glasgow Coma Scale, modified Rankin scale (mRS), and Barthel Index (BI) were recorded, and the cases were followed up for 90 days or till death. We looked at the risk factors associated with IS and ICH and functional outcome of IS vis-à-vis ICH using mRS and BI at 90 days postenrollment. We also compared the mortality of IS vis-à-vis ICH. Results: The presence of hypertension (100% vs. 88%) and smoking (50% vs. 26%) was significantly higher in ICH (P &lt; 0.05). The presence of diabetes mellitus (40% vs. 18%) and CAD (12% vs. 2%) was significantly more in IS cases (P &lt; 0.05). Consumption of alcohol was more prevalent in ICH patients compared to IS patients (30% vs. 24%). Based on mRS and BI at 90 days, ICH cases had significantly poorer functional outcome compared to IS cases (P &lt; 0.0001). Mortality of IS cases (4%) was also significantly less compared to ICH cases (30%). Conclusions: A combination of hypertension, smoking, and history of alcohol consumption had a higher predilection for the occurrence of ICH, whereas a combination of hypertension, diabetes mellitus, and CAD favored the occurrence of IS. The functional outcome of cases of ICH 90 days poststroke was significantly poorer compared to IS cases. The most important factors for poor outcome of ICH cases were more stroke severity at baseline compared to IS cases and the presence of intraventricular hemorrhages in some cases. Mortality was also found to be more in patients with ICH compared to IS.

Moderate elevation of serum uric acid levels improves short-term functional outcomes of ischemic stroke in patients with type 2 diabetes mellitus

BackgroundSerum uric acid (SUA), an end-product of purine catabolism diffused in the blood, is positively associated with the risk of type 2 diabetes mellitus (T2DM). However, in the T2DM population, the association of SUA fluctuation (DeltaSUA) with the functional outcome of ischemic stroke (IS) is still unclear. Accordingly, this study aimed to assess the correlation between DeltaSUA and short-term IS functional outcomes in T2DM patients.MethodsAll T2DM patients diagnosed with IS in the China National Stroke Registry III were included. DeltaSUA, which was defined as the difference between the SUA levels at baseline and 3 months after symptom onset, was classified into two groups, i.e., elevated DeltaSUA (DeltaSUA > 0) and reduced DeltaSUA (DeltaSUA le 0). The outcomes measured using the Modified Rankin Scale (mRS) were scored from 0 to 6, and poor functional outcome was defined as an mRS score of 3–6 at 3 months after IS.ResultsAmong the 1255 participants (mean age: 61.6 ± 9.8 years), 64.9% were men. Patients with elevated DeltaSUA had a lower incidence of poor functional outcomes at 3 months. Compared with reduced DeltaSUA, elevated DeltaSUA at 0–50 μmol/L (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.28–0.78, p = 0.004) and 50–100 μmol/L (OR = 0.40, 95% CI = 0.21–0.77, p = 0.006) was significantly correlated with a reduced risk of poor functional outcomes at 3 months.ConclusionThis study showed that a moderate increase in DeltaSUA in the range of 0–100 μmol/L at 3 months after IS might be beneficial in T2DM adults and more studies are warranted to confirm this.

The association between neutrophil counts and neutrophil-to-lymphocyte ratio and stress hyperglycemia in patients with acute ischemic stroke according to stroke etiology.

Stress hyperglycemia ratio (SHR), which is used to assess stress hyperglycemia, is associated with the functional outcome of ischemic stroke (IS). IS can induce the inflammatory response. Neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) as good and easily available inflammatory biomarkers, the relationship between neutrophil counts and NLR and SHR were poorly explored in IS. We aimed to systemically and comprehensively explore the correlation between various blood inflammation markers (mainly neutrophil counts and NLR) and SHR. Data from 487 patients with acute IS(AIS) in Xiangya Hospital were retrospectively reviewed. High/low SHR groups according to the median of SHR (≤1.02 versus >1.02). Binary logistic regression analysis was used to evaluate the correlation between neutrophil counts and NLR and high SHR group. Subgroup analyses were performed in the TOAST classification and functional prognosis. The neutrophil counts and NLR were all clearly associated with SHR levels in different logistic analysis models. In the subgroup analysis of TOAST classification, the higher neutrophil counts and NLR were the independent risk factors for high SHR patients with large-artery atherosclerosis (LAA) (neutrophil: adjusted OR:2.047, 95% CI: 1.355-3.093, P=0.001; NLR: adjusted OR:1.315, 95% CI: 1.129-1.530, P<0.001). The higher neutrophil counts were the independent risk factor for high SHR patients with cardioembolism (CE) (adjusted OR:2.413, 95% CI: 1.081-5.383, P=0.031). ROC analysis showed that neutrophil counts was helpful for differentiating high SHR group with CE and low SHR group with CE (neutrophil: AUC =0.776, P=0.002). However, there were no difference in levels of neutrophil counts and NLR between patients with SVO and without SVO. The higher neutrophil counts and NLR independently associated with high SHR patients with mRS ≤2 at 90 days from symptom onset, (neutrophil: adjusted OR:2.284, 95% CI: 1.525-3.420, P<0.001; NLR: adjusted OR:1.377, 95% CI: 1.164-1.629, P<0.001), but not in patients with mRS >2. This study found that the neutrophil counts and NLR are positively associated with SHR levels in AIS patients. In addition, the correlation between neutrophil counts and NLR and different SHR levels are diverse according to TOAST classification and functional prognosis.

Dipping Pattern and 1-year stroke functional outcome in ischemic stroke or transient ischemic attack

ABSTRACT Aims This study aimed to explore whether a relationship exists between dipping patterns and 1-year functional outcome in patients with acute ischemic stroke (IS) or transient ischemic attack (TIA). Methods Data from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke Study (BOSS), a nationwide, hospital-based, longitudinal cohort study, was used for this study. Patients with acute IS or TIA were recruited within 7 days after onset and ambulatory blood pressure monitoring was performed during hospitalization. Patients were defined as dippers if nocturnal systolic blood pressure fell by ≥10%, non-dippers if 0–10%, and reverse dippers if < 0%. Poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3–5. Logistic regression analysis was used to test the association between dipping patterns and 1-year functional outcome. Results Among the 1808 IS/TIA patients, 19.19% were dippers, 53.21% were non-dippers, and 27.60% were reverse dippers. Poor functional outcome occurred in 22.44% of reverse dippers, which was significantly higher than that of dippers (16.14%) and non-dippers (16.53%) (P = .014). A univariate analysis revealed that reverse dipping was a risk factor for poor functional outcome (Odds ratio 1.504, 95% confidence interval 1.055–2.145, P = .024). However, this significance disappeared after adjusting for confounders. Conclusions Reverse dipping was prevalent in patients with IS/TIA. The higher incidence of 1-year poor functional outcome in reverse dippers warrants further investigation.

ARTERIAL STIFFNESS GRADIENT PREDICTS INDEPENDENTLY FUNCTIONAL OUTCOME AFTER ISCHEMIC STROKE

Objective: Arterial stiffness is a strong predictor of morbidity in various clinical conditions, including ischemic stroke. However, the prognostic significance of the newly emerged aortic–brachial arterial stiffness gradient, defined as carotid–femoral/radial -carotid pulse wave velocity (PWV ratio) for functional outcome in ischemic stroke remains unknown. Design and method: We enrolled 144 patients (114 males, age 63.1 ± 12.4 years, mean ± SD) with acute ischemic stroke (NIHSS score at admission 6.6 ± 5.3 points). Carotid-femoral pulse wave velocity (PWV), radial –carotid PWV and peripheral blood pressure (BP) were measured (SphygmoCorâ) within several (6 ± 2) days after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale (mRS) with an mRS score of 3 to 6 (dependency or death) considered as a poor outcome. Results: PWV ratio was higher in patients with a poor stroke outcome than in patients of the reference group (1.34 ± 0.58 vs 1.17 ± 0.30; p = 0.017). In a multivariate analysis, the predictive value of PWV ratio remained significant (OR, 3.62; 95% CI, 1.04–12.75; p = 0.044) after adjustment for covariates. In contrast, CF PWV had no significant predictive value for stroke poor outcome. Conclusions: We found that the higher PWV ratio in patients in the subacute phase of ischemic stroke is independently associated with a poor outcome. This PWV index might be useful in clinical practice, including therapeutic decisions, but needs broader studies in patient populations of stroke subtypes.

Immunodepression, Infections, and Functional Outcome in Ischemic Stroke.

Stroke remains one of the main causes of mortality and morbidity worldwide. Immediately after stroke, a neuroinflammatory process starts in the brain, triggering a systemic immunodepression mainly through excessive activation of the autonomous nervous system. Manifestations of immunodepression include lymphopenia but also dysfunctional innate and adaptive immune cells. The resulting impaired antibacterial defenses render patients with stroke susceptible to infections. In addition, other risk factors like stroke severity, dysphagia, impaired consciousness, mechanical ventilation, catheterization, and older age predispose stroke patients for infections. Most common infections are pneumonia and urinary tract infection, both occur in ≈10% of the patients. Especially pneumonia increases unfavorable outcome and mortality in patients with stroke; systemic effects like hypotension, fever, delay in rehabilitation are thought to play a crucial role. Experimental and clinical data suggest that systemic infections enhance autoreactive immune responses against brain antigens and thus negatively affect outcome but convincing evidence is lacking. Prevention of poststroke infections by preventive antibiotic therapy did not improve functional outcome after stroke. Immunomodulatory approaches counteracting immunodepression to prevent stroke-associated pneumonia need to account for neuroinflammation in the ischemic brain and avoid further tissue damage. Experimental studies discovered interesting targets, but these have not yet been investigated in patients with stroke. A better understanding of the pathobiology may help to develop optimized approaches of preventive antibiotic therapy or immunomodulation to effectively prevent stroke-associated pneumonia while improving long-term outcome after stroke. In this review, we aim to characterize epidemiology, risk factors, cause, diagnosis, clinical presentation, and potential treatment of poststroke immunosuppression and associated infections.

Associations between RNA-Binding Motif Protein 3, Fibroblast Growth Factor 21, and Clinical Outcome in Patients with Stroke.

Background: RNA-binding motif protein 3 (RBM3) is a cold-induced marker of good functional outcome of ischemic stroke that is promising as a protective target. Fibroblast growth factor 21 (FGF21) is an obesity- and temperature-related hormone that upregulates the expression of RBM3, which is beneficial as a recombinant treatment and has been tested under different experimental pathological conditions, including stroke. However, the interaction between RBM3 and FGF21 has not yet been tested for clinical stroke conditions. Methods: In a sample of 66 stroke patients, we analyzed the associations between the FGF21 and RBM3 serum concentrations on admission and at 72 h, body weight, maximum temperature during the first 24 h, and the outcome of patients at 3 months. We also analyzed their association with biomarkers of obesity (adiponectin and leptin) and inflammation (interleukin-6 (IL-6) and interleukin (IL-10)). Results: Higher concentrations of FGF21 on admission and RBM3 at 72 h were associated with good outcomes. Serum FGF21 and RBM3 were directly related to body mass index and inversely related to the maximum temperature during the first 24 h. We found a positive association between the FGF21 concentrations in obese patients with leptin and a negative correlation with adiponectin in non-obese participants. Conclusions: This clinical study demonstrates the association between RBM3 and FGF21 levels and the outcome of stroke patients. Although further investigations are required, these data support the pharmacological induction of RBM3 as a promising protective therapy.

The Effect of Simvastatin on Acute Phase Functional Outcome of Ischemic Stroke

Introduction: Stroke is one of the leading causes of death and disability worldwide, and especially in Indonesia. Several studies showed the pleiotropic and neuroprotective effect of simvastatin in addition to lowering blood cholesterol levels. Objective: This trial was conducted to investigate if the administration of simvastatin in acute ischemic stroke management can improve functional outcomes. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in patients with acute ischemic stroke with an NIHSS score of 4-14. Participants were randomly assigned to receive 40 mg of simvastatin or placebo for seven days. The NIHSS scale was compared on admission day, 4th and 8th day after administration of simvastatin between the two groups. Results: 52 individuals were randomized: 28 to simvastatin and 24 to placebo. There was no significant improvement of functional outcome between the two groups (p &gt; 0.05). Conclusion: Administration of simvastatin had no significant effect on outcome (measured by NIHSS) in patients with acute ischemic stroke.

Impact of Pretreatment Ischemic Location on Functional Outcome after Thrombectomy.

Pretreatment ischemic location may be an important determinant for functional outcome prediction in acute ischemic stroke. In total, 143 anterior circulation ischemic stroke patients in the THRACE study were included. Ischemic lesions were semi-automatically segmented on pretreatment diffusion-weighted imaging and registered on brain atlases. The percentage of ischemic tissue in each atlas-segmented region was calculated. Statistical models with logistic regression and support vector machine were built to analyze the predictors of functional outcome. The investigated parameters included: age, baseline National Institutes of Health Stroke Scale score, and lesional volume (three-parameter model), together with the ischemic percentage in each atlas-segmented region (four-parameter model). The support vector machine with radial basis functions outperformed logistic regression in prediction accuracy. The support vector machine three-parameter model demonstrated an area under the curve of 0.77, while the four-parameter model achieved a higher area under the curve (0.82). Regions with marked impacts on outcome prediction were the uncinate fasciculus, postcentral gyrus, putamen, middle occipital gyrus, supramarginal gyrus, and posterior corona radiata in the left hemisphere; and the uncinate fasciculus, paracentral lobule, temporal pole, hippocampus, inferior occipital gyrus, middle temporal gyrus, pallidum, and anterior limb of the internal capsule in the right hemisphere. In conclusion, pretreatment ischemic location provided significant prognostic information for functional outcome in ischemic stroke.

Neutrophil to lymphocyte ratio, stroke severity and short term clinical outcomes in acute ischemic stroke

Background: Neutrophil to lymphocyte ratio is an easily evaluated systemic inflammation indicator. However, there are limited reports on neutrophil to lymphocyte ratio and functional outcome in ischemic stroke. In this study, we aimed to evaluate the association of neutrophil to lymphocyte ratio and stroke severity, short term functional outcomes and mortality in patients with acute ischemic stroke. Methods: The clinical data of patients who were &gt; 18 age-old and hospitalized with acute ischemic stroke in Baskent University Hospital, Ankara, Turkey between January 2018 and May 2019 were studied retrospectively. Neutrophil to lymphocyte ratio were measured. The neutrophil to lymphocyte ratio and National Institute of Health Stroke Scale (NIHSS) score at admission, mortality during hospitalization and Modified Rankin Scale (mRS) score at discharge of the patients with acute ischemic stroke were correlated. Results: Among the acute ischemic stroke patients due to the exclusion criteria, the data of 134 patients were evaluated. Median age of the patients were 76± 12.5 years and 82 patients (61.2%) were male. The median NIHSS scores of the patients at admission was 5±4.5. Mortality during the hospitalization was seen in 8 patients (6%). The median neutrophil to lymphocyte ratio value of the patients at admission were found to be 2.6±3.4. Neutrophil to lymphocyte ratio and NIHSS scores of the patients at admission, duration of the hospitalization, mRS scores at discharge and mortality during hospitalization were found to be positively correlated. Conclusion: Neutrophil to lymphocyte ratio is a simple and easily measured marker and can be used as a potential indicator for prognosis in acute ischemic stroke. However further prospective multicenter investigations are required to confirm the role of neutrophil to lymphocyte ratio for predicting the prognosis in acute ischemic stroke patients.

Minocycline and Magnesium As Neuroprotective Agents for Ischemic Stroke: A Systematic Review.

Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke. Minocycline (MC) and Magnesium (Mg) are promising therapies for ischemic stroke, especially in the pre-hospital setting. These drugs are readily available, inexpensive, and generally safe. We decided to investigate these drugs' neuroprotective effects in treating ischemic stroke in the acute and chronic setting. We conducted a systematic review of the published literature on MC and Mg's functional outcome in ischemic stroke. This paper's methodology included only clinical trials published in the last 15 years, using PubMed as a database. The systematic review demonstrated that MC infusion in the pre-hospital and hospital setting improved functional outcomes and disability scores.Furthermore, MC also decreased matrix metalloproteinase 9 (MMP-9) levels. MC might have a more significant effect on men than women because different molecular pathways of cerebral ischemia seem to be involved between both genders. The systematic review showed that patients with ischemic stroke did not benefit from magnesium sulfate infusion in the pre-hospital and hospital setting. Nevertheless, patients with lacunar strokes and patients who supplemented their meals with potassium-magnesium salt in the diet had better functional outcomes. Future studies would need a more significant sample of participants and a better selection to increase the study's power and avoid selection bias, respectively. Further publications could benefit from subcategorizing strokes and investigating the gender role in stroke treatment. These directives could give a more robust conclusion regarding the neuroprotective effects of these drugs.

New Index for Multiple Chronic Conditions Predicts Functional Outcome in Ischemic Stroke.

To determine whether a new index for multiple chronic conditions (MCCs) predicts poststroke functional outcome (FO), we developed and internally validated the new MCC index in patients with ischemic stroke. A prospective cohort of patients with ischemic stroke (2008-2017) was interviewed at baseline and 90 days in the Brain Attack Surveillance in Corpus Christi Project. An average of 22 activities of daily living (ADL)/instrumental ADL (IADL) items measured the FO score (range 1-4) at 90 days. A FO score >3 (representing a lot of difficulty with ADL/IADLs) was considered unfavorable FO. A new index was developed using machine learning techniques to select and weight conditions and prestroke impairments. Prestroke modified Rankin Scale (mRS) score, age, congestive heart failure (CHF), weight loss, diabetes, other neurologic disorders, and synergistic effects (dementia × age, CHF × renal failure, and prestroke mRS × prior stroke/TIA) were identified as important predictors in the MCC index. In the validation dataset, the index alone explained 31% of the variability in the FO score, was well-calibrated (p = 0.41), predicted unfavorable FO well (area under the receiver operating characteristic curve 0.81), and outperformed the modified Charlson Comorbidity Index in predicting the FO score and poststroke mRS. A new MCC index was developed and internally validated to improve the prediction of poststroke FO. Novel predictors and synergistic interactions were identified. This study provides Class II evidence that in patients with ischemic stroke, an index for MCC predicts FO at 90 days.

Untargeted metabolomics predicts the functional outcome of ischemic stroke

Metabolites in blood have been found associated with the occurrence of vascular diseases, but its role in the functional recovery of stroke is unclear. The aim of this study is to investigate whether the untargeted metabolomics at the acute stage of ischemic stroke is able to predict functional recovery. One hundred and fifty patients with acute ischemic stroke were recruited and followed up for 3 months. Fasting blood samples within 7 days of stroke were obtained, liquid chromatography and mass spectrometry were applied to identify outcome-associated metabolites. The patients' clinical characteristics and identified metabolites were included for constructing the outcome prediction model using machine learning approaches. By using multivariate analysis, 220 differentially expressed metabolites (DEMs) were discovered between patients with favorable outcomes (modified Rankin Scale, mRS≤2at 3 months, n=77) and unfavorable outcomes (mRS≥3at 3 months, n=73). After feature selection, 63 DEMs were chosen for constructing the outcome prediction model. The predictive accuracy was below 0.65 when including patients' clinical characteristics, and could reach 0.80 when including patients' clinical characteristics and 63 selected DEMs. The functional enrichment analysis identified platelet activating factor (PAF) as the strongest outcome-associated metabolite, which involved in proinflammatory mediators release, arachidonic acid metabolism, eosinophil degranulation, and production of reactive oxygen species. Metabolomics is a potential method to explore the blood biomarkers of acute ischemic stroke. The patients with unfavorable outcomes had a lower PAF level compared to those with favorable outcomes.

Serum Neurofilament Light Predicts Severity and Prognosis in Patients with Ischemic Stroke

Serum neurofilaments are markers of axonal injury. We investigated whether serum neurofilament light (sNfL) is a potential prognostic marker of functional outcome in Chinese patients with acute ischemic stroke (AIS). From May 2015 to December 2018, consecutive patients with AIS from the Department of Neurology of the Second Hospital of Jilin University were included. sNfL concentration was tested at baseline, and stroke severity was analyzed at admission using the NIHSS score. Functional outcome was assessed at discharge by the modified Rankin scale (mRS). The sNfL concentration was tested in 343 patients with a median value of 17.8 (IQR, 13.4-25.2) pg/ml. sNfL concentration paralleled lesion size (P = 0.035). At admission, 174 patients were defined as moderate-to-high stroke (NIHSS ≥ 5); the sNfL concentration in those patients were higher than that observed in patients with minor clinical severity [21.2 (IQR, 15.1-31.7) vs. 14.9 (11.8-19.4) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of moderate-to-high stroke increased by 202% (with the OR of 3.04 (95% CI 2.15-4.32), P < 0.001) and 102% [2.02 (1.10-3.16), P = 0.001), respectively. At discharge, 85 patients (24.8%) had poor functional outcome (mRS, 3-6); the sNfL concentration in those patients were higher than that observed in patients with good outcome [24.1 (IQR, 18.8-33.9) vs. 15.7 (11.9-21.8) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of poor outcome increased by 236% [with the OR of 3.36 (95% CI 2.23-5.06), P < 0.001] and 102% [2.29 (1.37-3.82), P < 0.001], respectively. The results show sNfL is meaningful blood biomarker to monitor stroke severity and functional outcome in ischemic stroke, suggesting that sNfL may play a role in stroke progression.

Associations Between Diffusion Dynamics and Functional Outcome in Acute and Early Subacute Ischemic Stroke.

The current study aimed to investigate the associations between diffusion dynamics of ischemic lesions and clinical functional outcome of acute and early subacute stroke. A total of 80 patients with first ever infarcts in the territory of the middle cerebral artery underwent multi-b-values diffusion-weighted imaging and diffusion kurtosis imaging. Multiple diffusion parameters were generated in postprocessing using different diffusion models. Long-term functional outcome was evaluated with modified Rankin scale (mRS) at 6 months post-stroke. Good functional outcome was defined as mRS score ≤ 2 and poor functional outcome was defined as mRS score ≥ 3. Univariate analysis was used to compare the diffusion parameters and clinical features between patients with poor and good functional outcome. Significant parameters were further analyzed for correlations with functional outcome using partial correlation. In univariate analyses, standard-b-values apparent diffusion coefficient (ADCst) ratio and fractional anisotropy (FA) ratio of acute stroke, ADCst ratio and mean kurtosis (MK) ratio of early subacute stroke were statistically different between patients with poor outcome and good outcome (P < 0.05). When the potential confounding factor of lesion volume was controlled, only FA ratio of acute stroke, ADCst ratio and MK ratio of early subacute stroke remained correlated with the functional outcome (P < 0.05). Diffusion dynamics are correlated with the clinical functional outcome of ischemic stroke. This correlation is independent of the effect of lesion volume and is specific to the time period between symptom onset and imaging. More effort is needed to further investigate the predictive value of diffusion-weighted imaging.

The Paradoxical Protective Effect of Liver Steatosis on Severity and Functional Outcome of Ischemic Stroke.

Background: There is very limited information on the relationship between non-alcoholic fatty liver disease (NAFLD) and the severity or functional outcomes of ischemic stroke or transient ischemic stroke (TIA). We investigated the correlation between NAFLD and stroke outcomes.Methods: NAFLD was assessed in 321 patients with first-ever acute ischemic stroke or TIA, who underwent transient elastography from January 2014 to December 2014. The association of liver steatosis with stroke severity, assessed using the National Institute of Health Stroke Scale (NIHSS), was investigated using robust regression analysis. We also compared the functional outcome at 90 days according to the presence or burden of liver steatosis.Results: NAFLD was observed in 206 (64.2%) patients. Patients with NAFLD had less severe stroke (median NIHSS score 2 vs. 3, P = 0.012) and more favorable functional outcome at 90 days (85.3 vs. 70.5, P = 0.004). Patients with NAFLD were likely to have a 23.3% lower [95% confidence interval (CI), −39.2 to −3.2%, P = 0.026] NIHSS score and a 2.5-fold higher (95% CI, 1.08–5.67, P = 0.033) possibility of favorable functional outcome in multivariate analysis.Conclusions: Our study shows that a higher burden of liver steatosis seems to be associated with less severe stroke and better functional outcome after ischemic stroke or TIA.

Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke

Background: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored. Methods: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome. Results: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4% and a specificity of 77.3% (area under the curve: .851, 95% confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value. Conclusions: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.